The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to reduce and prevent ischemic heart disease in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. More particularly, the present invention relates to the use of 17.alpha.-dihydroequilenin in atherosclerotic mammals and to evaluate its effects on plasma apolipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation.
Postmenopausal estrogen replacement therapy has gained wide recognition as a lifelong preventive regimen for the reduction of osteoporotic fracture and ischemic heart disease. Unfortunately, good scientific evidence has failed to persuade the majority of menopausal women that the benefits of long-term estrogen replacement therapy are worth the inconvenience or anxiety resulting from its side effects, especially vaginal bleeding and the putative increase in breast cancer risk. Additionally, most of the evidence of estrogenic effects in preventing ischemic heart disease in the United States is from studies that used unopposed conjugated equine estrogens. The current evidence is unclear as to whether the addition of progestins, necessary to prevent iatrogenically induced endometrial carcinoma, may either partially or completely negate the cardioprotective effect of unopposed estrogens. Several of the inventors have described a component of Premarin.RTM. (Wyeth-Ayerst, Princeton, N.J.), 17.alpha.-dihydroequilenin (DHEN), that caused no uterine hypertrophy in ovariectomized rats compared with ovariectomized controls and compared with a doubling of uterine weight in Premarin treated ovariectomized rats. [Washburn S A et al., A conjugated equine estrogen with differential effects on uterine weight and plasma cholesterol the rat. Am J Obstet Gynecol 1993;169:251-6]. It was determined that DHEN caused a 70% reduction in total plasma cholesterol concentrations compared with ovariectomized controls and compared with a 15% reduction of total plasma cholesterol in ovariectomized rats treated with oral Premarin.RTM..
Currently, there are no hormone replacement therapies that deliver established benefits to menopausal females and males such as the prevention and/or reduction of atherosclerotic heart disease without causing endometrial proliferation or other side effects of the type previously mentioned. Thus, there remains a need for an alternative hormone replacement therapy for menopausal women and men without side effects or the need to take concomitant progestin therapy.